Type CC Research Articles

Amplitude Parameters Are Predictive of Hearing Preservation in a Randomized Controlled Trial of Intracochlear Electrocochleography During Cochlear Implant Surgery.

To prospectively evaluate the association between hearing preservation after cochlear implantation (CI) and intracochlear electrocochleography (ECochG) amplitude parameters. Multi-institutional, prospective randomized clinical trial. Ten high-volume, tertiary care CI centers. Adults (n = 87) with sensorineural hearing loss meeting CI criteria (2018-2021) with audiometric thresholds of ≤80 dB HL at 500 Hz. Participants were randomized to CI surgery with or without audible ECochG monitoring. Electrode arrays were inserted to the full-depth marker. Hearing preservation was determined by comparing pre-CI, unaided low-frequency (125-, 250-, and 500-Hz) pure-tone average (LF-PTA) to LF-PTA at CI activation. Three ECochG amplitude parameters were analyzed: 1) insertion track patterns, 2) magnitude of ECochG amplitude change, and 3) total number of ECochG amplitude drops. The Type CC insertion track pattern, representing corrected drops in ECochG amplitude, was seen in 76% of cases with ECochG "on," compared with 24% of cases with ECochG "off" ( p = 0.003). The magnitude of ECochG signal drop was significantly correlated with the amount of LF-PTA change pre-CI and post-CI ( p < 0.05). The mean number of amplitude drops during electrode insertion was significantly correlated with change in LF-PTA at activation and 3 months post-CI ( p ≤ 0.01). ECochG amplitude parameters during CI surgery have important prognostic utility. Higher incidence of Type CC in ECochG "on" suggests that monitoring may be useful for surgeons in order to recover the ECochG signal and preventing potentially traumatic electrode-cochlear interactions.

Genetic analyses of truncated variant rs200185429 in ZNT8 encoding SLC30A8 gene with respect to prediabetes and type 2 diabetes in Bangladeshi population

Zinc transporter ZnT8, encoded by SLC30A8, is expressed highly in pancreatic β-cells that effluxes Zn2+ into insulin granules which is required to secret insulin from the granules. Genome-wide association study identified twelve loss of function mutations in SLC30A8 that play protective role against type 2 diabetes (T2D). This study aimed to find genetic association of a protein truncating variant rs200185429 in Bangladeshi healthy individuals (n = 184), patients with prediabetes (n = 130) and patients with T2D (n = 179). Genetic association study with respect to rs200185429 was performed using TaqMan® probe followed by allelic discrimination plots. Wild type CC genotype was found to be evenly distributed in healthy individuals (96.2 %), patients with prediabetes (95.38 %) and patients with T2D (94.41 %). CT genotype was more prevalent in T2D (5.59 %), less in healthy individuals (3.38 %). However, TT genotype was absent in the study participants. Mutant T allele was neither associated with prediabetes (OR = 1.22, χ2 = 0.12, p = 0.72) nor with T2D (OR = 1.42, χ2 = 0.52, p = 0.47). Similarly, none of the genetic inheritance models showed statistically significant association with T2D. Thus, a large-scale study is warranted to establish our finding regarding the association of rs200185429 with prediabetes and T2D in Bangladeshi population.

Linking insulin like growth factor-1 (IGF-1) rs6214 gene polymorphism and its serum level with risk of colorectal cancer

BackgroundColorectal Cancer is found one of the most profound type of cancer around globe, affecting men and women with different ethnic and racial groups. Insulin-like growth factor 1 is known as peptide growth factor found to increase the proliferation of cell and prevent apoptosis. Insulin pathway might have linked with progression of colorectal cancer.MethodsThis study conducted on total 160 subjects, including 80 patients with colorectal cancer with 80 age and gender match controls. Clinical parameters were compared between the control group and Colorectal cancer group. Blood serum IGF-1 was quantified by using ELISA and IGF-1 rs6214(C/T) variations were investigated using TaqMan allelic discrimination assay.ResultsBlood serum level of Insulin growth factor-I (ng/ml) showed substantial association concerning groups while IGF-1 rs6214(C/T) genotype distribution observed increased in colorectal cancer patients as compared to controls with significant association. The variant TT and CT genotype frequency observed more common in cases as compared to control. However, the wild type CC genotype were common in cases used to compared with controls. The Odds Ratio reveal the risk of variant IGF-1 rs6214 T allele to increase 3 times compared to wild type allele.ConclusionThe homozygous TT genotypes and T variant allele of IGF-1 rs6214(C/T) showed association with high serum Insulin growth factor level 1, may increase susceptibility to the colorectal cancer. This work will use to investigate the associations between Insulin-like growth factor 1 and rs6214(C/T) gene variant and blood serum level with the vulnerability to treat Colorectal. In summary, we have investigated the relationship between Insulin growth factor level hormone and colorectal cancer. Further studies are required to understand the association between colorectal cancer and polymorphism. However, this study can be serve as an informative study to uncover mechanisms behind main cause of colon cancer. Therefore, the genomic profiling of Insulin-like growth factor-1 can be helpful to treat colorectal cancer patients.

Role of metabolizing MTHFR gene polymorphism (rs1801133) and its mRNA expression among Type 2 Diabetes.

Type 2 Diabetes is a glucose metabolic disorder occurred by insulin insensitivity in which folate metabolism plays an important role. it is believed that polymorphism of Methylenetetrahydrofolate reductase (MTHFR) C677T linked with type 2 diabetes mellitus. However, results are conflicted. therefore, in this study we re-examine the relationship between MTHFR C677T in type 2 diabetes mellitus patients. Present research work included 100 newly diagnosed type 2 diabetic mellitus (T2DM) cases and 100 healthy individuals. After the blood sample collection all the biochemical parameters were evaluated among the T2DM cases and healthy individuals. DNA and RNA extraction from whole blood was done to study the MTHFR gene polymorphism by allele specific polymerase chain reaction method and its expression analysis was done by quantitative real time polymerase chain reaction method. The significant difference was observed in genotype distribution among case and control group (p=0.0002). Compared with wildtype CC genotype, CT heterozygous (OR=2.95, 95% Cl=1.62-5.38) and TT homozygous (OR=3.20, CI=1.79-5.73) suggest to have effect of MTHFR polymorphism on type 2 mellitus risk. Moreover, relative MTHFR mRNA expression was found for wild type CC genotype 3.02-fold, CT heterozygous genotype 2.57 fold and mutant TT homozygous genotype 0.50-fold which is down regulated (p<0.0001). Our results indicates that the polymorphism in MTHFR C677T plays significant role in type II diabetes risk. MTHFR CT heterozygous and mutant TT genotype showed reduced mRNA expression among the T2DM patients. However, large scale case-control studies are needed to strengthen such conclusion in the future.

MYD88 Gene Polimorphism in Patients With Chronic Lenfoid Leukemia

Leukemia is a type of cancer that manifests itself with the excessive proliferation of blood cells, especially white blood cells, and affects the blood production system in the body. Leukemias are classified as acute or chronic and according to the extent and development of the tumor. In chronic lymphocyte leukemia (CLL), cancer cells are found in the bone marrow, blood, and lymph nodes. Therefore, in this study, the effects of polymorphisms in the MYD88 gene of CLL patients were investigated. For this purpose, 100 patients diagnosed with CLL and 70 healthy individuals without cancer history were included in the study as the control group. DNA was isolated from CLL patients and control groups. Polymorphisms in the MYD88 (L265p T/C) promoter regions were studied by RT-PCR. Genotype and allele frequencies were calculated directly. Statistical significance of genotypic distributions between CLL patients and control groups was evaluated with Z Ratios test and Fisher's Exact test.For the MYD88 L265p T/C region in 100 CLL patients, 95 wild type TT, 3 TC and 5 mutant type CC genotypes were detected. No statistically significant difference was found between CLL patients and control groups in the MYD88 L265p T/C region (p 0.05). According to the allele frequencies of the region, it was determined as 0.965 and 0.065 for T and C, respectively. According to Fisher's Exact results, it was calculated as 0.078 for TT, 0.078 for TC and 0.269 for Mutant, respectively. The MYD88 genotype frequencies of the patients included in the study do not appear to be statistically correlated with CLL patients. The research we have done as a result of our study will shed light on the studies with different SNPs to be made with the increase in the number of CLL patients..

Spatially resolved properties of supernova host galaxies in SDSS-IV MaNGA

We crossmatch galaxies from Mapping Nearby Galaxies at Apache Point Observatory with the Open Supernova Catalog, obtaining a total of 132 SNe within MaNGA bundle. These 132 SNe can be classified into 67 Type Ia and 65 Type CC. We study the global and local properties of supernova host galaxies statistically. Type Ia SNe are distributed in both star-forming galaxies and quiescent galaxies, while Type CC SNe are all distributed along the star-forming main sequence. As the stellar mass increases, the Type Ia/CC number ratio increases. We find: (1) there is no obvious difference in the interaction possibilities and environments between Type Ia SN hosts and a control sample of galaxies with similar stellar mass and SFR distributions, except that Type Ia SNe tend to appear in galaxies which are more bulge-dominated than their controls. For Type CC SNe, there is no difference between their hosts and the control galaxies in galaxy morphology, interaction possibilities as well as environments; (2) compared to galaxy centers, the SN locations have smaller velocity dispersion, lower metallicity, and younger stellar population. This is a natural result of radius gradients for all these parameters. The SN location and its symmetrical position relative to the galaxy center, as well as regions with similar effective radii have very similar [Mg/Fe], gas-phase metallicity, gas velocity dispersion and stellar population age.

Evaluation of divalent metal transporter 1 (DMT1) (rs224589) polymorphism on blood lead levels of occupationally exposed individuals

Lead (Pb) is an environmental and public health toxicant. It affects various organ systems of the body, thereby disrupting their normal functions. To date, several genes that are known to influence the mechanism of action of lead and toxicity have been studied. Among them, the iron transporter gene, SLC11A2 (Solute Carrier 11 group A member 2) which codes for the transmembrane protein, DMT1 (Divalent Metal Transporter 1) has shown to transport other metals including zinc, copper, and lead. We investigated the influence of DMT1 polymorphism (rs224589) on blood lead (Pb-B) levels. In the present study, we enrolled 113 lead-exposed workers and performed a comprehensive biochemical analysis and genetic composition. The frequency of DMT1 variants observed in the total subjects (n = 113) was 42 % for homozygous CC wild type, 54 % for heterozygous CA, and 4 % for homozygous AA mutant. The heterozygous CA carriers presented higher Pb-B levels compared to wild type CC and mutant AA carriers. Further, a negative association was observed between Pb-B levels and hemoglobin in heterozygous CA carriers. Hence, C allele may be the risk allele that contributes to increased susceptibility to high Pb-B retention, and genotyping of DMT1 in lead exposed subjects might be used as a prognostic marker to impede organ damage due to lead toxicity.

Conventional I-shape brace member bolted connections under seismic loading: Laboratory study

In many regions of the world, a conventional low-ductility concentrically braced frame (CBF) is commonly chosen as the seismic force resisting system. The energy dissipation is not restricted to yielding and buckling of the braces, as would be required for ductile braced frames; rather, energy dissipation is assumed to occur through localised yielding and friction in connections, as well as limited member yielding. The objective of this study was to characterize by means of laboratory testing the inelastic response of full-scale conventional I-shape braces and their bolted connections under reversed-cyclic seismic loading. Six brace specimens comprising two commonly used bolted connection types, flange plate and flange angle, were designed following the Type CC provisions prescribed by CSA S16. The brace specimens achieved storey drift ratios of 1%–2%, due to inelastic deformations in both the braces and the connections, even though capacity based design provisions were not incorporated in their design. Energy dissipation resulted from overall and local brace buckling, gusset plate buckling, tension yielding of flange plates, angles and gusset plates, block shear failure of brace webs and angles, bolt fracture and fracture of the gusset plates, along with bolt slip. However, the observed performance of these braces and connections in this laboratory based study is not necessarily guaranteed to be replicated for all conventional CBF designs due to the conservative nature and variability in accuracy of the existing CSA S16 design equations that were relied upon to design and detail the test specimens.

Seismic response and design of steel multi-tiered concentrically braced frames of the conventional construction category in moderate seismic regions of Eastern Canada

This study examines the seismic behaviour of steel multi-tiered concentrically braced frames (MT-CBFs) of the conventional construction category (Type CC) in moderate seismic regions of eastern Canada and proposes a new seismic design method for such structures. A total of 32 prototype MT-CBFs part of a single-storey building are selected and designed in accordance with the 2019 Canadian steel design standard (CSA S16-19) provisions for Type CC structures, excluding the design requirements prescribed for frames taller than 15 m, namely the amplification of seismic forces varying by the frame height and the amplification of the column factored seismic force. Nonlinear response history analyses are then performed to examine their seismic response. The results confirmed that tiers experience limited lateral deformation, intermediate horizontal struts are required between tiers, and columns are subjected to combined axial force and bi-axial bending, which in some cases led to column buckling. The results are used to propose a new seismic design method in the framework of CSA S16.

Constraining neutrino mass in dark energy dark matter interaction and comparison with 2018 Planck results

In this paper, we investigate the constraints on the total neutrino mass sum m_{nu } in a cosmological model in which dark energy and neutrinos are coupled such that the mass of the neutrinos and potentials are function of the scalar field as m_{nu }=m_{0}exp (frac{alpha phi }{m_{pl}}) and V(phi )=m_{pl}^{4}exp (frac{-lambda phi }{m_{pl}}) respectively. The observational data used in this work include the type Ia supernovae (SN) observation (Pantheon compilation), CC, CMB and BAO data. We find that the neutrino mass is tightly constrained to sum m_{nu }< 0.125 eV 95% Confidence Level (C.L.) and the effective extra relativistic degrees of freedom to be N_{eff}=2.955^{+0.11}_{-0.12} 68% C.L in agreement with the Standard Model prediction N_{eff} = 3.046, matter-radiation equality, z_{eq}=3389^{+24}_{25} (68% C.L). These results are in good agreement with the results of Planck 2018 where the limit of the total neutrino mass is sum m_{nu }<0.12 eV (95% C.L., TT, TE, EE + lowE + lensing + BAO) , N_{eff}=2.99^{+0.17}_{-0.17} (68% C.L., TT, TE, EE + lowE + lensing + BAO) and z_{eq}=3387^{+21}_{21} (68% C.L TT, TE, EE + lowE + lensing + BAO).

An Experimental Comparison of the Effects of Nanocrystalline Core Geometry on the Performance and Dispersion Inductance of the MFTs Applied in DC-DC Converters

The development of Medium Frequency Transformers (MFTs) from a novel perspective is essential for the advancement of today´s various relevant applications such as the emerging solid-state transformers, along with interfaces for the interconnection of photovoltaic parks and electric vehicles. The analysis, design and implementation of MFTs pursuing the achievement of characteristics such as high power density, high efficiency, and a specific dispersion inductance is a key goal for designers. There are several parameters and design methods that influence the final performance of an MFT, such as the geometry and material of the core. The advantages/disadvantages of each material/geometry combination, about the dispersion inductance for instance, are not well known, even considering a single material but various geometries. This paper presents the analysis, design and experimental development of three nanocrystalline-core MFTs, each one with a different core geometry (toroidal, type CC and shell-type). The purpose of this work is to evaluate and compare the most favourable characteristics and performance of each type of geometry, tested at 5 kHz and 1.75 kVA. The cases studied, in simulation and experimentation with scaled prototypes, focus on evaluating the power density, the core losses, the winding losses, the geometric dimensions, and the dispersion inductance obtained in each MFT, as well as its performances operating with sinusoidal and square waveforms. The results show that: 1) the toroid core has higher efficiency; 2) the shell core has the lowest dispersion inductance and is easier to build, and 3) the CC type has the highest dispersion inductance. This new information is a step to further understand how to get more controllable, more efficient MFTS, with a higher power density and lower cost, depending on the intended application of cutting-edge DC-DC DAB-type converters.

Short-term prognosis of childhood hepatoblastoma in relation to ERCC1 C118T single nucleotide polymorphism and VEGF expression.

To evaluate the short-term prognosis of pediatric hepatoblastoma (HB) in relation to excision repair cross-complementation gene 1 (ERCC1) C118T single nucleotide polymorphism (SNP) and VEGF expression. ERCC1 C118T SNP and VEGF expression were detected and investigated in 31 children with HB undergoing platinum-based chemotherapy, to analyze their relationship with short-term pediatric HB prognosis. CC (38.7%; 12/31), CT (35.5%; 11/31), and TT (25.8%; 8/31) ERCC1 C118T mutation types were identified. The Kaplan-Meier survival curve analysis showed that the CC group had a better short-term prognosis than the CT + TT group (p = 0.010). VEGF was overexpressed in 14 cases (45.2%) and underexpressed in 17 cases (54.8%). The Kaplan-Meier survival curve analysis showed that the high VEGF expression group showed poorer short-term prognosis than the lower VEGF expression group (p = 0.004). In this study, ERCC1 C118T SNP in children with HB was mainly found to be mutant type CT + TT. Compared to wild type CC, children with the mutant type CT + TT exhibited better treatment efficacy and remission with platinum-based chemotherapy as well as better survival rates. Moreover, the short-term prognosis of children with low VEGF expression was better than in those with high expression.

Improved Canadian seismic provisions for steel braced frames in heavy industrial structures

The seismic provisions of the Canadian CSA S16-14 standard for steel structures for heavy industrial steel structures are reviewed and applied for a 65.4 m tall concentrically braced frames (CBFs) for an industrial application in Vancouver, BC. Two approaches are examined: a capacity design method in accordance with CSA S16 Annex M and a simpler, non-capacity design approach for the structures of the Conventional Construction (Type CC) category. Nonlinear response history analyses are performed to examine and compare the seismic response of the structures. Modifications are proposed to mobilize higher brace inelastic response, mitigate storey drift concentrations, and ensure that the columns can safely resist the seismic induced axial and flexural demands. The modified provisions are validated for additional structures having heights varying from 43 to 80 m and two different vertical distribution of the seismic weights. The robustness of the structures against excessive storey drifts and column buckling limit states is verified through incremental dynamic analysis. Both Annex M and Type CC design approaches, as modified in this study, represent two practical options to achieve cost-effective designs resulting in satisfactory seismic response. Three-dimensional nonlinear response history analysis is used to compare the 100%–100% and 100%–30% combination rules to predict the axial load demand on columns part of two orthogonal CBFs. For the structure studied, the results showed that the latter would give more realistic force estimates.

Clinical outcomes of gastric cancer patients received capecitabine based adjuvant chemotherapy and the corresponding pharmacogenomics analysis

Objective: To investigate the association between Thymidine phosphorylase(TYMP)genetic variation and clinical outcomes of postoperative gastric cancer (GC) patients received capecitabine based regimens. Methods: A total of 198 GC patients underwent surgical treatment and received capecitabine based adjuvant chemotherapy were included in this retrospective study. Peripheral blood and the postoperative tissue specimen of the GC patients were collected for the genotyping of polymorphism and TYMP mRNA expression, respectively. The correlation between polymorphism and clinical outcomes and safety of postoperative GC patients were analysed. Results: Located in the upstream, rs11479 was of clinical significance. The prevalence of rs11479 in TYMP among the GC patients were as follows: CC genotype 125 cases (63.13%), CT genotype 65 cases (32.83%), TT genotype 8 cases (4.04%), minor allele frequency of rs11479 is 0.20. The distribution of three genotypes were in accordance with Hardy-Weinberg Equilibrium (P=0.901). The analysis results of patients with different genotypes found that the 3-year disease free survival rate of the patients with CT/TT genotype and CC genotype were 73.97% and 65.60%, respectively, which was statistically significant (P=0.003). In terms of overall survival, the 3-year overall survival rate of the two genotypes were 83.56% and 72.80% (P=0.012), respectively. Adjusted in multivariate Cox regression analysis, CT/TT genotype was an independent favorable factor for disease free survival (OR=0.55, P=0.011). Safety analysis indicated that there was no significant association between genotypes and grade 2 adverse reaction. Additionally, of the 79 postoperative tissue specimens, the results showed that the expression of TYMP in cancer tissues of the patients with CT/TT genotypes were significantly higher than those of the wild type CC genotype patients (P<0.001). Conclusion: The polymorphism rs11479 of TYMP have favorable influence on the clinical outcomes of gastric cancer patients received capecitabine based adjuvant chemotherapy treatment through changing the mRNA expression of TYMP.

The influence of Thymidine Phosphorylase genetic variation on clinical outcomes and safety of colorectal cancer patients received adjuvant chemotherapy after R0 resection

Objective: To study the association between Thymidine Phosphorylase (TYMP) genetic variation and clinical outcomes and safety of postoperative colorectal cancer (CRC) patients. Methods: A total of 235 patients with colorectal cancer underwent surgical treatment were included in this retrospective analysis. Peripheral blood and the postoperative tissue specimen of the CRC patients were collected for the genotyping of polymorphism and TYMP mRNA expression, respectively. The correlation between polymorphism and clinical outcomes and safety of postoperative CRC patients were analysed. Results: Located in the upstream, 5633C>T was of clinical significance. The prevalence of 5633C>T in TYMP among the CRC patients were as follows: CC genotype 149 cases (63.40%), CT genotype 73 cases (31.06%), TT genotype 13 cases (5.54%), minor allele frequency of 5633C>T is 0.21. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.313). CT genotype and TT genotype patients were merged in the comparison of prognosis. The survival analysis of patients with different genotypes found that the median Overall Survival (OS) of CT/TT genotype and CC genotype were 5.8 and 4.5 year, which was statistically significant (P=0.009). Adjusted in multivariate Cox regression analysis, CT/TT genotype was an independent favorable factor for OS (HR=0.67, P=0.015). Additionally, of the 87 postoperative tissue specimens, the results showed that the expression of TYMP in cancer tissues of the patients with CT or TT genotypes were significantly higher than those of the wild type CC genotype patients (P=0.019). And the safety analysis showed that the incidence of grade 3 hand-foot syndrome among CT/TT genotype patients were higher than that of CC genotype patients (33.72% vs 20.13%, OR=1.68, P=0.021). Conclusion: The polymorphism 5633C>T of TYMP may impact the prognosis of CRC patients received adjuvant chemotherapy by influencing the mRNA expression of TYMP.

The role of ABCC2 gene in drug-resistant epilepsy

Objective To investigate the role of the ATP binding box C subfamily 2 transporter protein (ABCC2) gene in drug-resistant epilepsy. Methods From February 2014 to February 2018, 204 epileptic patients were treated in our hospital, including 41 cases of drug resistance epilepsy (drug resistance group), 163 cases of non drug resistant epilepsy (sensitive group). The rs717620 polymorphism of ABCC2 gene and the level of P- glycoprotein (P-gp) in cerebrospinal fluid and serum were detected in two groups. Results The proportion of genotype TT and gene frequency T in the drug resistant group were 24.39% and 41.46%, respectively, which were significantly higher than those in the sensitive group (P 0.05); The concentration of P-gp in cerebrospinal fluid of patients with genotype TT in drug resistance group was (24.03±3.57)ng/ml, which was significantly higher than that of type CC and CT (P 0.05). Conclusions The rs717620 polymorphism of ABCC2 gene may be associated with drug-resistant epilepsy, and may be related to P-gp level in the cerebrospinal fluid. Key words: Multidrug resistance-associated proteins/GE; Polymorphism, single nucleotide; Epilepsy

Vibration-Induced Errors in MEMS Tuning Fork Gyroscopes with Imbalance.

This paper discusses the vibration-induced error in non-ideal MEMS tuning fork gyroscopes (TFGs). Ideal TFGs which are thought to be immune to vibrations do not exist, and imbalance between two gyros of TFGs is an inevitable phenomenon. Three types of fabrication imperfections (i.e., stiffness imbalance, mass imbalance, and damping imbalance) are studied, considering different imbalance radios. We focus on the coupling types of two gyros of TFGs in both drive and sense directions, and the vibration sensitivities of four TFG designs with imbalance are simulated and compared. It is found that non-ideal TFGs with two gyros coupled both in drive and sense directions (type CC TFGs) are the most insensitive to vibrations with frequencies close to the TFG operating frequencies. However, sense-axis vibrations with in-phase resonant frequencies of a coupled gyros system result in severe error outputs to TFGs with two gyros coupled in the sense direction, which is mainly attributed to the sense capacitance nonlinearity. With increasing stiffness coupled ratio of the coupled gyros system, the sensitivity to vibrations with operating frequencies is cut down, yet sensitivity to vibrations with in-phase frequencies is amplified.

The effect of the first-generation HCV-protease inhibitors boceprevir and telaprevir and the relation to baseline NS3 resistance mutations in genotype 1: experience from a small Swedish cohort

Background: The clinical experience with protease-inhibitor (PI) triple regimen appears disappointing regarding effect, side effects, high work load, and costs. This real-world study evaluates baseline and emerging resistance-associated substitutions (RASs) and their significance for treatment outcome.Method: Thirty-six genotype 1a/b patients treated according to Swedish recommendations during 2011–2013 with triple therapy including pegylated interferon and ribavirin in combination with a protease-inhibitor, either boceprevir (BOC) or telaprevir (TVR), were retrospectively evaluated. Frozen serum samples from the patients were tested for resistance with pan-genotypic population sequencing.Results: Overall, 56% (20/36) of the patients achieved sustained viral response (SVR). The SVR was comparable between BOC (64%; 9/14) and TVR (50%; 11/22) (p = 0.07), and the IL28B type non-CC (48%; 12/25) and CC (46%; 6/13) (p = 0.77). The SVR was higher in patients without cirrhosis (89.5%; 17/19) (p < 0.0005), in treatment-naïve patients (70%; 14/20) (p = 0.02), and those with low viral load (<800,000 IU/mL) (66.7%; 8/12) (p < 0.0002), compared to those with cirrhosis (17.6%; 3/17), treatment-experienced (37.5%; 6/16), and high viral load (>800,000 IU/mL) (50%; 12/24).Conclusion: PI triple regimes were highly effective in treatment-naïve patients without cirrhosis, but in this real-world cohort an inferior effect was evident in cirrhotic and treatment-experienced patients. Although tested on a limited sample, the baseline resistance testing seems to have no impact on prediction of therapy outcome. The reason could be that the baseline RASs T54S and V55A have relatively low resistance towards BOC and TVR. Emerging RASs, mainly R155K, with known high resistance to BOC and TVR were frequently found in non-responders.

Mutations in inhibin alpha gene and their association with litter size in Kalahari Red and Nigerian goats

This study was conducted to identify SNPs in inhibin alpha (INHA) gene and investigate their association with litter size in two Nigerian goat breeds {West African Dwarf (WAD, n = 226), Red Sokoto (RS, n = 70)} and Kalahari Red (KR, n = 70). Sequence analyses revealed four SNPs {g.−65C > G/rs643347356 (5’UTR), g.2518G > A (a novel variant in exon 2), g.3041A > G/rs641311609 (exon 3) and g.3234C > T/rs670889338 (3’UTR)}. Homozygous wild type CC at g.−65C > G and GG at g.2518G > A loci were predominant genotypes in Kalahari Red goats. CC was the predominant genotype in all the three breeds at g.3234C > T locus and the frequency of allele C was 0.88, 0.98 and 0.98 in WAD, RS and KR populations respectively. Allele diversity index was low (He < 0.3) in the three breeds at g.−65C > G, g.2518G > A and g.3234C > T loci. WAD and KR goats had moderate genetic diversity (0.25 ≤ PIC ≤ 0.5) at g.3041A > G locus. Pair-wise comparison revealed that does having CT genotype at g.3234 C> T locus had significantly (P = 0.01) larger litter size compared with CC in WAD goats, while SNP genotype at other loci were not significantly associated with litter size.

Impact of VKORC1 gene polymorphisms on warfarin maintenance dosage: A novel systematic review and meta-analysis of 53 studies.

To analyze the correlation between <i>VKORC1</i> gene polymorphisms and warfarin maintenance dosage, as well as the correlation of dosage of warfarin with age and ethnicity. We retrieved related studies published between January 2000 and March 2016 from PubMed, Embase, the Cochrane Library, Web of Science, VIP, CNKI, and Wan Fang data. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and crosscheck data. Then, RevMan5.3 software was used to perform a meta-analysis. 53 studies were included in the meta-analysis. The most prevalent genotypes were -1639 AA, 1173 TT, and 3730 GG in both Asian and Caucasians, but the distribution frequencies of all three were higher in Asians than in Caucasians. The meta-analysis showed that compared with homozygous <i>VKORC1</i>-1639 AA carriers, carriers of type GA, GG, and G (GA + GG) required 45% (95% confidence interval (CI) 42-49), 77% (95% CI 70-84), and 51% (95% CI 47-55) higher warfarin doses, respectively. Carriers of type CC, TC, and C (CC + TC) required 83% (95% CI 73-92), 26% (95% CI 23-29), and 53% (95% CI 44-62) higher warfarin doses, respectively, compared to homozygous <i>VKORC1</i> 1173 TT carriers. Carriers of type AA, GA, and A (AA + GA) required 40% (95% CI 29-51), 25% (95% CI 17-33), and 33% (95% CI 21-45) higher warfarin doses, respectively, compared to carriers of the homozygous <i>VKORC1</i> 3730 GG polymorphism (all p<0.05). Subgroup analysis showed that Asian patients aged ≤60 years carrying 1173 CC, TC, and C genotypes required 28%, 39%, and 22% higher warfarin doses, respectively, compared with patients aged >60 years. Caucasian patients aged >60 years carrying -1639 GA, GG and G genotypes needed 24%, 39%, and 37% lower warfarin doses, respectively, compared with patients aged ≤60 years. These differences were statistically significant (p<0.05). Our study showed that the relationship between <italic>VKORC1</italic> gene polymorphisms and warfarin maintenance dose differs between individuals, and that individuals with different ages and ethnicities require different doses of warfarin. Caucasians carriers of genotype -1639 GG, G and 1173 CC, TC, C required a higher mean daily warfarin doses compared with Asian patients. Therefore, in order to achieve optimal treatment and lowest risk, <i>VKORC1</i> gene polymorphism detection is suggested. .